Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, United States.
Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, United States.
Mol Cell Neurosci. 2018 Sep;91:3-9. doi: 10.1016/j.mcn.2018.03.004. Epub 2018 Mar 12.
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane. In this review, we consider mechanisms of trafficking of AMPA receptors to and from synapses that take place in the early trafficking stages, starting in the endoplasmic reticulum (ER) and continuing into the secretory pathway. We consider mechanisms of AMPA receptor assembly in the ER, highlighting the role of protein synthesis and the selective properties of specific AMPA receptor subunits, as well as regulation of ER exit, including the roles of chaperones and accessory proteins and the incorporation of AMPA receptors into COPII vesicles. We consider these processes in the context of the mechanism of mGluR LTD and discuss a compelling role for the dendritic ER membrane that is found proximal to synapses. The review illustrates the important, yet little studied, contribution of the early stages of AMPA receptor trafficking to synaptic plasticity.
大脑的一个基本特性是其能够根据自身活动来改变功能。这种自我调节能力在很大程度上取决于突触可塑性。现在人们已经认识到，对于兴奋性突触，突触可塑性的很大一部分取决于从神经末梢释放的谷氨酸引起的突触后反应的变化。突触后反应的改变反过来又取决于突触后膜中 AMPA 受体的丰度变化。在这篇综述中，我们考虑了 AMPA 受体在早期运输阶段从突触到突触的运输机制，该阶段始于内质网 (ER) 并延续到分泌途径。我们考虑了 ER 中 AMPA 受体组装的机制，强调了蛋白质合成的作用以及特定 AMPA 受体亚基的选择性特性，以及 ER 出口的调节，包括伴侣蛋白和辅助蛋白的作用以及 AMPA 受体整合到 COPII 小泡中。我们在 mGluR LTD 机制的背景下考虑这些过程，并讨论了在突触附近发现的树突状 ER 膜的重要但研究甚少的作用。该综述说明了 AMPA 受体运输的早期阶段对突触可塑性的重要但研究甚少的贡献。
